The development of efficient synthetic routes to biologically important small molecules constitutes the major focus of the grant application. In the majority of the studies outlined herein, the reactive dipole, a nitrile oxide, will be added in either an intramolecular or intermolecular fashion to an alkene to furnish a substituted isoxazoline. By properly processing the isoxazoline, access to either a Gamma-amino alcohol or a Beta-hydroxy ketone can be achieved. The following topics represent the specific objectives to be accomplished during the requested grant period: (1) Ergot Alkaloid (used in treatment of hypertension, migrane attacks, postpartum hemorrhage etc.) Studies: (a) develop a route to lysergic acid; (b) prepare other ergots from a common precursor; (c) synthesize clavicipitic acid and aurantioclavine (biological properties unknown); (d) examine an ene route to Alpha-cyclopiazonic acid (mycotoxin); (e) synthesize possible biogenetic precursors to the ergolines for feeding studies; (2) Five-membered Ring Synthesis: (a) examine a route to protaglandins (tissue hormones); (b) use the diasteroselective intramolecular nitrile oxide cycloaddition (INOC) reaction to prepare integerrinecic acid and a fragment of macbecin (antitumor activity); (c) ascertain the ability of homoallylic and bis-homoallylic asymmetric centers to control diastereoface selectivity in the INOC reaction - prepare a fragment of palytoxin; (3) Develop an INOC Route to Mitomycins (antitumor activity); (4) Develop an INOC Route to Morphine (narcotic analgesic); (5) Develop a (3+2) approach to C-Nucleosides (antibiotic, antiviral and antitumor activity); (6) Develop a Chiral-Selective Syn-Carboxyhydroxylation Process.